The neutrophil plays an important role in both innate immunity and in inflammatory reactions in human disease (Burg et al., Clin. Immunol. 99, 7-17 (2001)). The neutrophil eliminates invading microorganisms through phagocytosis, generation of reactive oxygen metabolites and release of microbicidal substances stored in different granules in neutrophil. Apart from secretory vesicles, neutrophils contain azurophil, specific (secondary) and gelatinase-containing granules (tertiary) (Borregaard et al., Blood 89, 3503-3521 (1997)) formed in the bone marrow at subsequent stages of neutrophil maturation (Borregaard et al., Blood 85, No 3, 812-817 (1995)). During neutrophil-mediated inflammatory reactions the secretory vesicles are mobilized first upon stimulation, followed by the tertiary, the secondary and the azurophil granules (Sengelov et al., J. Immunol. 154, 4157-4165 (1995); and Sengelby et al. J. Immunol. 150 No. 4, 1535-1543 (1993)). Upon phagocytosis, the azurophil granules fuse with the phagosomes, which causes the release of proteolytic and bactericidal factors into the phagolysosome, where the invading microorganism is killed and digested (Burg et al., (2001) cited above).
Phospholipase Bs (Ghannoum et al., Clin. Microbiol. Rev. 13, 122-43, Table (2000)) are a heterogeneous group of enzymes that can hydrolyze both the sn-1 and sn-2 fatty acids of glycerophospholipids, and thus display both phospholipase A1 or phospholipase A2 and lysophospholipase activities. Several PLBs have been identified in various microorganisms (Ghannoum et al., (2000) cited above; and (Farn et al., J. Bacteriol. 183, 6717-6720 (2001)), fungi (Ghannoum et al., (2000) cited above), Dictystelium discoideum (Ferber et al., Eur. J. Biochem. 14, 253-257 (1970)) and in the brush border membrane of mature enterocytes from guinea pig (Gassama-Diagne et al., J. Biol. Chem. 267, 13418-13424 (1992)), rat (Tojo et al., J. Biol. Chem. 273, 2214-2221 (1998), rabbit (Boll et al., J. Biol. Chem. 268, 12901-12911 (1993)) and human epidermis (Maury at al., Biochem. Biophys. Res. Commun. 295, 362-369 (2002)). PLBs are also important components of venoms from bees and snakes. Bacterial and fungal PLBs have been reported to be virulence factors that damage host cells, while PLBs of enterocytes from mammals are involved in digestion of dietary lipids, and PLB expressed in human epidermis probably plays a role in the differentiation process and is involved in the epidermal barrier function.
The full length of the FLJ22662 protein comprises 552 amino acid residues (SEQ ID NO: 1, AAH63561). A recombinantly produced FLJ22662 protein containing a sequence of 223 residues from the full length variant (a.a 330-552) (AAH00909, Strausberg et al., Proc. Natl. Acad. Sci. U.S.A. 99 (26), 16899-16903 (2002)) fused to GST is commercially available from Novus Biologicals (Littleton Colo., US). Suggested uses are Western blot, ELISA, and assay development. US patent applications 20070059717, 20070004038, 20060252056, 20060240426, 20060199204, 20060194199, 20060111314, 20060073496, 20060046259, 20060019256, 20050208500, 20050095607, 20040076955, 20040005563, 20030170743, and 20030165949 (issued as U.S. Pat. No. 7,189,507) are related to the diagnosis and therapy of various diseases and mention FLJ22662 proteins and their genes as one out of many other proteins that might be of interest.
All US patents and patent applications including published International patent applications designating the US are hereby incorporated in their entirety into the present specification.